Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury ...Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.展开更多
The effect of myocardium being subjected to 60 min ischemia and 60 min reperfusion incat cardiopulmonary bypass on level of lipid peroxides(LPO),function of myocardial mitochon-dria and activity of superoxides dismuta...The effect of myocardium being subjected to 60 min ischemia and 60 min reperfusion incat cardiopulmonary bypass on level of lipid peroxides(LPO),function of myocardial mitochon-dria and activity of superoxides dismutase(SOD)was studied. Myocardial mitochondrial functionwas depressed slightly 60 rain after ischemia but significantly 60 min after reperfusion.Increasedlipid peroxides content and decreased activity of SOD were observed at 60 rain after ischemia.Af-ter reperfusion,the activity of SOD continued decreasing,and LPO elevated still further.Theseresults support the hypothesis that free radicals may contribute to myocardial reperfusion injury.展开更多
OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) us...OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.展开更多
It is known that reperfusion injury occurs after reperfusion with normal blood in ischemic myocardium. Using the cat cardiopulmonary bypass model, this study documented that myocardial mitochondrial function was sigmf...It is known that reperfusion injury occurs after reperfusion with normal blood in ischemic myocardium. Using the cat cardiopulmonary bypass model, this study documented that myocardial mitochondrial function was sigmficantly depressed 60min after reperfusion, but was only slightly depressed in the controlled reperfusion group. Significantly increased MDA content and decreased activity of SOD was observed 60 min after reperfusion, whereas in the controlled reperfusion group, the MDA content was low and the activity of SOD was protected. These results indicate that controlled reperfusion with warm blood cardioplegia containing mannitol after ischemia provides benefit in avoiding myocardial mitochondrial reperfusion injury by preventing or reducing a potentially harmful component of reperfusion.展开更多
基金Supported by the National Natural Science Foundation of China(Nos.30700884,30873145)the Distinguished Middle-aged and Young Scientist Encourage and Reward Foundation of Shandong Province,China(No.BS2009SW015)
文摘Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.
文摘The effect of myocardium being subjected to 60 min ischemia and 60 min reperfusion incat cardiopulmonary bypass on level of lipid peroxides(LPO),function of myocardial mitochon-dria and activity of superoxides dismutase(SOD)was studied. Myocardial mitochondrial functionwas depressed slightly 60 rain after ischemia but significantly 60 min after reperfusion.Increasedlipid peroxides content and decreased activity of SOD were observed at 60 rain after ischemia.Af-ter reperfusion,the activity of SOD continued decreasing,and LPO elevated still further.Theseresults support the hypothesis that free radicals may contribute to myocardial reperfusion injury.
文摘OBJECTIVE To determine the functional role of hydrogen sulfide(H_2S) in protecting against mitochondrial dysfunction in heart failure through the inhibition of Ca^(2+)/calmodulin-dependent protein kinaseⅡ(Ca MKⅡ) using wild type and CSE knockout mouse models.METHODS Continuous subcutaneous injection isoprenaline(7.5 mg·kg^(-1) per day),once a day for 4 weeks to induce heart failure in male C57BL/6(6-8 weeks old) mice and CSE-/-mice.150 μmol·L^(-1) H_2O_2 was used to induce oxidative stress in H9c2 cells.Echocardiograph was used to detect cardiac parameters.H&E stain and Masson stain was to observation histopathological changes.Western blot was used to detect protein expression and activity.The si RNA was used to silence protein expression.HPLC was used to detect H_2S level.Biotin assay was used to detect the level of S-sulfhydration protein.RESULTS Treatment with S-propyl-L-cysteine(SPRC) or sodium hydrosulfide(Na HS),modulators of blood H_2S levels,attenuated the development of heart failure in animals,reduced lipid peroxidation,and preserved mitochondrial function.The inhibition Ca MKⅡ phosphorylation by SPRC and Na HS as demonstrated using both in vivo and in vitro models corresponded with the cardioprotective effects of these compounds.Interestingly,Ca MKⅡ activity was found to be elevated in CSE-/-mice as compared to wild type animals and the phosphorylation status of Ca MK Ⅱ appeared to relate to the severity of heart failure.Importantly,in wild type mice SPRC was found to promote S-sulfhydration of Ca MKⅡ leading to reduced activity of this protein however,in CSE-/-mice S-sulfhydration was abolished following SPRC treatment.CONCLUSION A novel mechanism depicting a role of S-sulfhydration in the regulation of Ca MKⅡ is presented.SPRC mediated S-sulfhydration of Ca MKⅡ was found to inhibit Ca MKⅡ activity and to preserve cardiovascular homeostasis.
文摘It is known that reperfusion injury occurs after reperfusion with normal blood in ischemic myocardium. Using the cat cardiopulmonary bypass model, this study documented that myocardial mitochondrial function was sigmficantly depressed 60min after reperfusion, but was only slightly depressed in the controlled reperfusion group. Significantly increased MDA content and decreased activity of SOD was observed 60 min after reperfusion, whereas in the controlled reperfusion group, the MDA content was low and the activity of SOD was protected. These results indicate that controlled reperfusion with warm blood cardioplegia containing mannitol after ischemia provides benefit in avoiding myocardial mitochondrial reperfusion injury by preventing or reducing a potentially harmful component of reperfusion.
